Effect of Chinese herbal medicine suppositories for hyperemesis gravidarum
by using an index for nausea and vomiting of pregnancy

Introduction

Hyperemesis gravidarum is a clinical condition in which pernicious vomiting
of pregnancy, which is manifested chiefly by gastrointestinal symptoms, leads
to deterioration and impaired intake of meals, nutritional and metabolic disturbances,
and a status requiring treatment.

The current therapeutic modality for hyperemesis gravidarum is palliative treatment
which is based on fluid therapy. There are many patients who fail to be improved
by fluid therapy alone. Since hyperemesis gravidarum develops in coincidence
with the phase of organogenesis in the early stages of pregnancy, antiemetics
are generally not administered. Chinese herbal medicines, which are considered
effective and safe for morning sickness and hyperemesis gravidarum in East Asia,
present some disadvantages when ingested orally, e.g., induction of nausea because
of their characteristic odour. Because of the above reason, we formulated and
used suppositories of Chinese herbal medicine extracts. The chief symptoms of
hyperemesis gravidarum are subjective, making it difficult to compare the symptoms
and evaluate efficacy of treatment. In the present clinical trial, therefore,
we categorised symptoms by severity and evaluated therapeutic efficacy according
to a questionnaire-based survey using the Index for Nausea and Vomiting of Pregnancy
(INVP), Table 1.

Table 1

Methods

PatientsThe present clinical trial was conducted from April, 1997 to August, 1998
for pregnant women in whom ultrasonography confirmed heart beats of the foetus
in the uterine cavity, who showed nausea or vomiting, and who gave consent to
the use of Chinese medicine extract suppositories.

Preparation of Chinese Herbal Medicine SuppositoriesHard fat (1.5 g, Witepsol S55) was melted by warming and used as the base.
Subsequently, 1.25 g of Chinese herbal medicine extract granules were mixed
with the base, and the mixture was stirred well. The mixture was then poured
into a suppository mould and cooled to obtain solid suppositories.

Two suppositories were equivalent to one dose of oral extract. Although these
Chinese herbal medicine suppositories differ little from the commercial ones
in terms of both shape and size, their colour is dark brown. The suppositories
were stored in a cool place.

The following Chinese herbal medicine extracts were used: TSUMURA Hange-koboku-to
Extract Granules for Ethical Use (TJ-16) as Suppository HKT; and TSUMURA Bukuryon-in-go-hange-koboku-to
Extract Granules for Ethical Use (TJ-116) as Suppository BIH.

Usage of Chinese Herbal Medicine Suppositories
The Chinese herbal medicine suppositories were used in combination with fluid
therapy. H2-receptor antagonists were also administered intravenously for reflux
oesophagitis and gastritis. One or two suppositories were inserted into the
anus 30 minutes before each meal and at bedtime.

Suppository HKT was used as the drug of first choice for patients who had nausea
or vomiting. Suppository BIH was used for patients who showed symptoms of reflux
oesophagitis or gastritis.

Items of Examination
To evaluate the efficacy of the Chinese herbal medicine suppositories, a questionnaire-based
survey, on the basis of the INVP, was conducted after the termination of the
present clinical trial. The questionnaire required the selection of the options
in Table 1 in terms of symptoms found before and after treatment.

The INVP values represented the total score of six items in terms of the symptoms
that were found before and after treatment. Symptoms were categorised as follows:
"less than mild", when INVP values were 2 points or lower; "mild",
when the INVP values were 3 to 6 points; "moderate", when INVP values
were 7 to 12 points; and "severe", when the INVP values were 13 to
18 points.

Categories for the Efficacy of the Treatment
The efficacy of the treatment was categorised as follows: "excellent effect",
when the INVP values, being 3 points or higher before treatment, decreased to
2 points or lower after treatment; "good effect", when the INVP values,
being 3 points or higher before treatment, decreased to 2 points or higher after
treatment; and "poor effect", when the INVP values remained unchanged
or increased after treatment.

Patient Groups
There were three patient groups: Group I of outpatients; Group II of patients
who were hospitalised due to hyperemesis gravidarum (showing no complications
other than gastritis and reflux oesophagitis); and Group III of patients who
were hospitalised due to threatened abortion (showing symptoms of hyperemesis
during hospitalisation).

Each group was further divided into the subgroups of Suppository HKT and Suppository
BIH. The patients, for whom the suppository was changed from HKT to BIH, were
considered as patients who used suppository BIH.

Statistical Analysis
The Wilcoxon test was used to evaluate the efficacy of the treatment, with a
significant difference at p = 0.05.

Results

The number of patients in whom the suppositories were used were as follows:
21 for HKT and two for BIH in Group I; 13 for HKT and 13 for BIH in Group II;
and five for HKT and one for BIH in Group III. Of these, the number of patients
who replied to the questionnaire were as follows: 16 for HKT and one for BIH
in Group I; 10 for HKT and 13 for BIH in Group II; and five for HKT and one
for BIH in Group III.

The INVP values before and after treatment are shown in Figure 1. The means
of the INVP values in Group I were 9.4 ± 3.0 points and 4.1 ±
2.3 points; in Group II they were 13.1 ± 4.0 points and 4.3 ±
4.0 points; and in Group III they were 8.7 ± 3.4 points and 4.3 ±
1.5 points before and after treatment. Therefore, a significant difference was
found in all groups.

Figure 1 - INVP Values Before and After Treatment

Furthermore, the means of the INVP values by drug were as follows: for HKT,
10.0 ± 4.0 points before treatment and 4.0 ± 2.5 points after
treatment; and for BIH, 12.9 ± 4.0 points before treatment and 4.0 ±
2.8 points after treatment. Therefore, a significant difference was found in
the total scores which were determined before and after treatment.

Six patients had side effects using the suppositories; all side effects were
watery diarrhoea. Two of these patients discontinued using the suppository.

Discussion

It is difficult to evaluate hyperemesis gravidarum objectively, because of
the fact that it mainly consists of subjective symptoms. Furthermore, the number
of classes of the complaints considered to be symptoms of hyperemesis gravidarum
is as numerous as 20. Based on the above background, the Emesis Index (EI) has
been created, modified and used. The EI originally created chiefly consisted
of three symptoms of high incidence and intense severity, i.e., nausea, vomiting,
and appetite. The INVP, modified to include the symptoms of salivation and dryness
of mouth and acetone in the urine, was used in the present clinical trial. The
INVP is thought to be more useful than the EI for evaluating hyperemesis gravidarum.

Fluid therapy was combined in treating many cases. Suppositories alone were
used in the majority of outpatients and in the inpatients who detested the odour
of the fluid. These patients showed no particular problems, and the improving
process of symptoms did not differ from the patients in whom fluid therapy was
combined. In the patients in whom fluid therapy was used alone and in combination
with suppositories, symptoms improved earlier at the time of combined therapy
than at the time of fluid therapy alone.

Herbal remedies are recommended commonly for nausea and vomiting of pregnancy.1
Chinese herbal medicine suppositories appear to be a reasonable therapeutic
alternative for hyperemesis gravidarum. A randomised trial is needed to confirm
the efficacy of Chinese herbal medicine suppositories for hyperemesis gravidarum.